The proposed study will examine the extent to which, among Hispanic youth, the effects of culturally related stressors on alcohol/drug use and conduct problems are mediated by physiological stress responses. Prior work has established the psychosocial and biological pathways through which physiological stress responses potentiate alcohol/drug use and conduct problems. What is not known is the extent to which cultural stressors, over and above other sources of stress, predict physiological stress responses, and whether cultural stressors exert an indirect effect on alcohol/drug use and conduct problems through physiological stress responses. This question is important for prevention science because few interventions have been developed to offset the effects of cultural stressors, and our results will provide essential information regarding whether such interventions are needed – as well as the protective mechanisms on which such interventions should focus. We propose a 3-year accelerated longitudinal cohort study with two cohorts, one beginning in the seventh grade and one beginning in the ninth grade, to carry out the study aims and to test the study hypotheses. An accelerated longitudinal design includes multiple age cohorts, where each cohort starts at a different age and each is followed for the same amount of time. Such a design allows us to examine five years of development through only three years of data collection. We will recruit and follow 300 Hispanic 7th and 9th graders in Los Angeles and Miami-Dade counties. Adolescents will be followed for 3 years and assessed at both macro (longer measures administered every 6 months) and micro (daily measurement bursts using shorter measures and saliva sample collection for cortisol assays). We will examine the moderating effects of three evidence- based protective mechanisms – family functioning, life skills, cultural assets, and ethnic socialization – on the direct and mediated effects of cultural stress on physiological stress responses and on alcohol/drug use and conduct problems. These moderation and moderated mediation analyses will indicate the specific mechanisms that should be targeted within prevention programs. This information is critical to decreasing disparities in conduct problems and alcohol/drug use among Hispanic adolescents.